Most genera of new world primates exhibit vitamin D resistance, i.e., insensitivity that may be characterized biochemically by the maintenance of high circulating concentration of the active vitamin D metabolite 1,25 dihydroxy vitamin D3, Gacad et al J. Bone Min. Res. 8:27-35 (1993). Humans and old world primates, on the other hand, do not exhibit vitamin D resistance. This vitamin D resistance phenomenon in new world primates is also correlated with high circulating levels of other steroid hormones including glucocorticoid (Chrousos et al Endocrinology 115:25-32 (1984), Lipsett et al Recent Prog. Hormone Res. 42:199-246 (1985), Brandon et al Cancer Res. 49:2203-2213 (1989)), mineral corticoid, progesterone, testosterone, 17.beta.-estradiol (Chrousos et al J. Clin. Endocrinol. Metab. 58:516-920 (1984)), 1,25-(OH).sub.2 D (Takahashi et al Biochem S. 227:555-563 (1985)).
By gaining an understanding of the biochemical mechanisms behind vitamin D resistance and the high levels of circulating steroid hormones in new world primates, new opportunities for treating and diagnosing diseases related to either over-production or under-production of vitamin D and other steroidal hormones may be achieved. Such diseases include osteoporosis, hypercalcemia, and vitamin D intoxication, hypersecretion of steroid hormones, and the like.
Vitamin D receptors bind to the consensus vitamin D response element as described in Ozono et al J. Biol Chem. 265:21881-21888 (1990). The invention described herein relates to the discovery of a novel protein that inhibits that binding of vitamin D receptor to vitamin D receptor binding element. By inhibiting the binding of the vitamin D receptor to vitamin D response elements, it is possible to modulate the expression of genes regulated by estrogen via vitamin D receptors. Vitamin D and vitamin D receptors play a significant role in the etiology of many diseases such as osteoporosis and some cancers, e.g. tumors that include hypercalcemia. It is thus of interest to provide proteins that interact with vitamin D response elements and polynucleotides encoding such proteins.